Substituted isoxazolo pyridinones

ABSTRACT

This disclosure describes novel compounds of the formula ##STR1## where R 1  is straight chain lower alkyl, and 
     R 2  and R 3  independently represent hydrogen or lower alkyl or together with N represent ##STR2## where X is CH 2 , O or N--CH 3 , and 
     R 4  is hydrogen, halo having an atomic weight of about 19 to 36 or lower alkoxy which are useful as hypolipidemic agents.

This is a division of application Ser. No. 705,702, filed July 15, 1976,now U.S. Pat. No. 4,049,813.

This invention relates to substituted isoxazolo pyridinones whichexhibit hypolipidemic activity. In particular, it relates to3-substituted-5-methyl-6-substituted-isoxazolo-[4,5-c]pyridin-4(5H)-ones,intermediates thereof and pharmaceutically acceptable salts.

The compounds of this invention may be represented by the followingstructural formula ##STR3## where R₁ is straight chain lower alkyl,i.e., straight chain lower alkyl having 1 to 4 carbon atoms, e.g.,methyl, ethyl, propyl and the like, and

R₂ and R₃ each independently represent hydrogen or lower alkyl, i.e.,alkyl having 1 to 4 carbon atoms, e.g., methyl, ethyl, isopropyl and thelike, or together with N represent ##STR4## where X is CH₂,O, or N--CH₃,and

R₄ is hydrogen, halo having an atomic weight of about 19 to 36 or loweralkoxy, i.e., alkoxy having 1 to 4 carbon atoms, e.g., methoxy, ethoxy,propoxy and the like.

The compounds of formula (I) are prepared according to the followingreaction scheme: ##STR5## where Z represents chlorine or bromine, and

R₁, r₂, r₃ and R₄ are as defined above.

The compounds of formula (I) are prepared by reacting a compound of theformula (II) with a compound of the formula (III) in the presence of aninert organic solvent. Although the particular solvent employed is notcritical, the preferred solvents include the halogenated hydrocarbonssuch as methylene dichloride, chloroform, carbon tetrachloride and thelike or the aromatic hydrocarbons such as benzene, toluene and the like,preferably toluene. The temperature of the reaction is not critical, butit is preferred that the reaction be run from about 20° to 150° C.,preferably from about 30° to 60° C. The reaction is run from about 10 to30 hours, preferably from about 16 to 24 hours. The product is recoveredusing conventional techniques, e.g., filtration followed by evaporation.

The compounds of formula (II) are prepared according to the followingreaction scheme: ##STR6## where Z, R₁ and R₄ are as defined above.

The compounds of formula (II) are prepared by treating a compound of theformula (IV) with a halogenating agent in the presence of an inertorganic solvent and free radical initiation. Although the particularhalogenating agent employed is not critical, it is preferred that thereaction be run in the presence of chlorine, bromine,N-chlorosuccinimide, N-bromosuccinimide, N-bromo phthalimide,N-bromo-acetamide, and the like, preferably N-bromosuccinimide. In thepreferred process, the free radical initiator used is an organic orinorganic peroxide, especially benzoylperoxide. The reaction can also becarried out under ultraviolet light. Although the particular solventused is not critical, the preferred solvents include the aromatichydrocarbons such as benzene, toluene and the like or the halogenatedhydrocarbons such as methylene dichloride, chloroform or carbontetrachloride, the latter being especially preferred. The temperature ofthe reaction is not critical, but it is preferred that the reaction berun from about 60° to 150° C., preferably the reflux temperature of thesolvent. The reaction is run from about 1 to 10 hours, preferably fromabout 2 to 9 hours. The resulting product was identified by NMRanalysis.

The compounds of formula (IV) are prepared according to the followingreaction scheme: ##STR7## where R₁ and R₄ are as defined above.

The compounds of formula (IV) are prepared by treating a compound of theformula (V) with an acid, such as hydrochloric acid, p-toluenesulfonicacid, polyphosphoric acid or sulfuric acid, the latter being especiallypreferred, in the presence of an inert solvent. Although the particularsolvent employed is not critical, the preferred solvents include thearomatic hydrocarbons, such as benzene, toluene and the like, or anexcess of the acid utilized above, the latter being especiallypreferred. The temperature of the reaction is not critical, but it ispreferred that the reaction be run from about 80° to 150° C., preferablythe reflux temperature of the solvent. The reaction is run from about 12to 36 hours, preferably from about 20 to 36 hours. The product isrecovered using conventional techniques, e.g., trituration followed byrecrystallization.

The compounds of formula (V) are prepared according to the followingreaction scheme: ##STR8## where R₁ and R₄ are as defined above.

The compounds of formula (V) are prepared by treating a compound of theformula (VI) with an oxidizing agent such as chromium trioxide,potassium permanganate, and the like, preferably chromium trioxide,under acidic conditions in the presence of water and acetone. Althoughthe particular acid employed is not critical, the preferred acidsinclude the mineral acids such as acetic acid, hydrochloric acid orsulfuric acid, the latter being especially preferred. The particularsolvent employed is not critical, and depending upon the oxidizing agentutilized above, may include acetone, pyridine and the like, preferablyacetone. The temperature of the reaction is not critical, but it ispreferred that the reaction be run from about 0° to 50° C., preferablyfrom about 20° to 30° C. The reaction is run from about 1 to 10 hours,preferably from about 2 to 4 hours. The product is recovered usingconventional techniques, e.g., trituration followed by filtration.

The compounds of formula (VI) are prepared according to the followingreaction scheme: ##STR9## where R₁ and R₄ are as defined above.

The compounds of formula (VI) are prepared by treating a compound of theformula (VII) with a compound of the formula (VIII) in the presence ofan inert organic solvent. Although the particular solvent employed isnot critical, the preferred solvents include an ether such asdiethylether or tetrahydrofuran or an aliphatic hydrocarbon such aspentane, hexane, heptane and the like, preferably tetrahydrofuran. Thetemperature of the reaction is not critical, but it is preferred thatthe reaction be run at a temperature of from about -75° to -55° C.,preferably from about -65° to -60° C. The reaction is run from about 1to 5 hours, preferably from about 2.5 to 3.5 hours. The product isrecovered using conventional techniques, e.g., trituration followed byfiltration.

The compounds of formula (VII) are prepared according to the followingreaction scheme: ##STR10## where R₅ is lower alkyl having 1 to 4 carbonatoms, and

R₁ and R₄ are as defined above.

The compounds of formula (VII) are prepared by treating a compound ofthe formula (IX) with a compound of the formula (X) in the presence ofan inert organic solvent. Although the particular solvent employed isnot critical, the preferred solvents include an ether such asdiethylether or tetrahydrofuran or an aliphatic hydrocarbon such aspentane, hexane, heptane and the like, preferably hexane. Thetemperature of the reaction is not critical, but it is preferred thatthe reaction be run at a temperature of from about -75° to -55° C.,preferably from about -65° to -60° C. The reaction is run from about 1to 5 hours, preferably from about 2.5 to 3.5 hours. The compound offormula (VII) is not isolated but employed in situ as a startingmaterial in the preparation of the compounds of formula (VI).

Many of the compounds of formulae (III), (VIII), (IX) and (X) are knownand may be prepared by methods described in the literature. Thecompounds of formulae (III), (VIII), (IX) and (X) not specificallydescribed may be prepared by analogous methods from known startingmaterials.

The compounds of formula (I) are useful because they possesspharmaceutical activity in animals as hypolipidemic agents, as indicatedby the fall in cholesterol and triglyceride levels in male albino Wistarrats weighing 110-130 g. initially. The rats are maintained on drug-freelaboratory chow diet for 7 days and then divided into groups of 8 to 10animals. Each group with the exception of the control is then givenorally 120 milligrams per kilogram of body weight per diem of thecompound for 6 days. At the end of this period, the animals areanesthetized with sodium hexobarbital and bled from the carotidarteries. Serum or plasma samples are collected, and 1.0 ml. samples ofthe serum are added to 9.0 ml. redistilled isopropanol. Two autoanalyzercupsful of a mixture of zeolite-copper hydroxide and Lloydds reagent(Kessler, G., and Lederer, H., 1965, Technicon Symposium, Mediad Inc.,New York, [345-347]) are added, and the mixture is shaken for 1 hour.Cholesterol and triglyceride levels are determined simultaneously on thesame sample by Technicon N 24 A (cholesterol) and N-78 (triglyceride)methodology. The mean total serum cholesterol levels are then computedand the hypocholesterolemic activity is expressed as the fall incholesterol levels as a percentage of the control level. The change inserum triglyceride levels induced by the drug is computed as apercentage of the control triglyceride levels.

For such usage, the compounds (I) may be combined with apharmaceutically acceptable carrier or adjuvant and may be administeredorally or parenterally as such or admixed with conventionalpharmaceutical carriers. They may be administered in such forms astablets, dispersible powders, granules, capsules, syrups, and elixirsand parenterally as solutions, suspensions, dispersions, emulsions andthe like, e.g., a sterile injectable aqueous solution. The dosage willvary depending upon the mode of administration utilized and theparticular compound employed.

The compounds of formula (I) may be similarly administered in the formof their non-toxic pharmaceutically acceptable salts. Such salts possessthe same order of activity as the free base and are readily prepared byreacting the base with an appropriate acid by conventional techniquesand, accordingly, are included within the scope of this invention.Representative of such salts are the mineral acid salts, e.g.,hydrochloride, hydrobromide, sulfate and the like.

The hypolipidemic effective dosage of these active compounds in thealleviation of lipidemia may vary depending on the particular compoundemployed and the severity of the condition being treated. However, ingeneral, satisfactory results are obtained when the compounds of formula(I) are administered at a daily dosage of from about 4.0 milligrams toabout 250 milligrams per kilogram of animal body weight, preferablygiven in divided doses two to four times a day, or in sustained releaseform. For most large mammals, the total daily dosage is from about 250milligrams to about 1000 milligrams. Dosage forms suitable for internaluse comprise from about 62.5 to about 500 milligrams of the activecompound in intimate admixture with a solid or liquid pharmaceuticallyacceptable carrier or diluent.

A representative formulation suitable for oral administration 2 to 4times a day for the treatment of lipidemia is a capsule prepared bystandard encapsulating techniques which contains the following:

    ______________________________________                                        Ingredients            Weight (mg.)                                           ______________________________________                                        5-methyl-3-phenyl-6-(p-[dimethyl-                                             aminomethyl]phenyl)-isoxazolo                                                 [4,5-c]pyridin-4(5H)-one                                                                             150                                                    inert solid diluent (starch, lactose,                                         kaolin)                300                                                    ______________________________________                                    

EXAMPLE 13-Phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

A suspension of 75 g. (0.348 mole) of3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide and 1 liter oftetrahydrofuran is cooled to -65° C. and 478 ml. of 1.6M n-butyllithiumin hexane (0.765 mole) is added dropwise maintaining the temperaturebetween -60° and -70° C. After the addition is complete, the orangesuspension is stirred for 11/2 hours at -60° to -70° C., and then 37.2g. (0.350 mole) of p-tolualdehyde in 375 ml. tetrahydrofuran is addeddropwise maintaining the temperature between -60° and -70° C. Afteraddition is complete the mixture is stirred for 11/2 hrs. at -60° to-70° C. and then warmed to -30° C. and quenched by the addition ofsaturated ammonium chloride solution. The mixture is further dilutedwith tetrahydrofuran and the layers are separated. The tetrahydrofuranlayer is washed twice with 50% brine, and once with brine, dried overanhydrous magnesium sulfate, filtered and evaporated in vacuo. The solidresidue is triturated with a 50:50 mixture of ether:petroleum ether,filtered and washed with cold ether to give3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide;m.p. 148° to 150° C.

Following the above procedure and using in place of3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide an equivalent amount of

a. 3-(p-chlorophenyl)-5,N-dimethyl-isoxazole-4-carboxamide,

b. 3-(p-fluorophenyl)-5,N-dimethyl-isoxazole-4-carboxamide,

c. 3-(p-anisyl)-5,N-dimethyl-isoxazole-4-carboxamide

there is obtained

a.3-(p-chlorophenyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

b.3-(p-fluorophenyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,or

c.3-(p-anisyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,respectively.

Again following the above procedure but using in place ofp-tolualdehyde, an equivalent amount of

d. o-tolualdehyde or

e. m-tolualdehyde

there is obtained

d.3-phenyl-5-(2-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamideor

e.3-phenyl-5-(3-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,respectively.

EXAMPLE 2 N-methyl-5-(4-methylphenacyl)-3-phenyl-4-isoxazole carboxamide

A mixture of 41.4 g. (0.123 mole) of3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamideand 800 ml. of acetone is treated dropwise with the addition of 92.5 ml.(0.185 mole) of Jones reagent [100 g. chromium trioxide, 160 ml.concentrated sulfuric acid with water to 500 ml.] and the resultingmixture is stirred at room temperature for 2 hours. The supernatantliquid is decanted and the solvent removed in vacuo, the residue istaken up in water/methylene chloride and the layers separated. Theorganic phase is washed with saturated sodium chloride solution, driedover anhydrous magnesium sulfate, filtered and evaporated in vacuo. Theresidue is treated with ether to give a solid and then triturated withethanol to give N-methyl-5-(4-methylphenacyl)-3-phenyl-4-isoxazolecarboxamide.

Following the above procedure and using in place of3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,an equivalent amount of

a.3-(p-chlorophenyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

b.3-(p-fluorophenyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

c.3-(p-anisyl)-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

d.3-phenyl-5-(2-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,or

e.3-phenyl-5-(3-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

there is obtained

a. N-methyl-5-(4-methylphenacyl)-3-(p-chlorophenyl)-4-isoxazolecarboxamide,

b. N-methyl-5-(4-methylphenacyl)-3-(p-fluorophenyl)-4-isoxazolecarboxamide,

c. N-methyl-5-(4-methylphenacyl)-3-(p-anisyl)-4-isoxazole carboxamide,

d. N-methyl-5-(2-methylphenacyl)-3-phenyl-4-isoxazole carboxamide, or

e. N-methyl-5-(3-methylphenacyl)-3-phenyl-4-isoxazole carboxamide,respectively.

EXAMPLE 35-Methyl-3-phenyl-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one

A mixture of 26.1 g. (0.0815 mole) ofN-methyl-5-(4-methylphenacyl)-3-phenyl-4-isoxazole carboxamide and 261ml. of 2M sulfuric acid is refluxed for 24 hours. The mixture is cooledand extracted with methylene chloride. The methylene chloride layer iswashed with water and then brine, dried over anhydrous magnesiumsulfate, filtered and evaporated in vacuo. The residue is trituratedwith ether and then recrystallized from ethanol to give5-methyl-3-phenyl-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one; m.p.155° to 156° C.

Following the above procedure and using in place ofN-methyl-5-(4-methylphenacyl)-3-phenyl-4-isoxazole carboxamide, anequivalent amount of

a. N-methyl-5-(4-methylphenacyl)-3-(p-chlorophenyl)-4-isoxazolecarboxamide,

b. N-methyl-5-(4-methylphenacyl)-3-(p-fluorophenyl)-4-isoxazolecarboxamide,

c. N-methyl-5-(4-methylphenacyl)-3-(p-anisyl)-4-isoxazole carboxamide,

d. N-methyl-5-(2-methylphenacyl)-3-phenyl-4-isoxazole carboxamide, or

e. N-methyl-5-(3-methylphenacyl)-3-phenyl-4-isoxazole carboxamide,

there is obtained

a.5-methyl-3-(p-chlorophenyl)-6-(p-tolyl)-isoxazole[4,5-c]pyridin-4(5H)-one,

b.5-methyl-3-(p-fluorophenyl)-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

c. 5-methyl-3-(p-anisyl)-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

d. 5-methyl-3-phenyl-6-(o-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one, or

e. 5-methyl-3-phenyl-6-(m-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,respectively.

EXAMPLE 45-Methyl-3-phenyl-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one

A mixture of 34.9 g. (0.110 mole) of5-methyl-3-phenyl-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one, 21.6 g.(0.121 mole) N-bromosuccinimide and 0.1 g. benzoyl peroxide in 500 ml.carbon tetrachloride is refluxed for 2 hours. The resulting mixture iscooled and the solid filtered and washed with more carbon tetrachloride.The solvent is then removed in vacuo and the resulting solid isdetermined by NMR to contain 62% of5-methyl-3-phenyl-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one.

Following the above procedure and using in place of5-methyl-3-phenyl-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one anequivalent amount of

a.5-methyl-3-(p-chlorophenyl)-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

b.5-methyl-3-(p-fluorophenyl)-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

c. 5-methyl-3-(p-anisyl)-6-(p-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

d. 5-methyl-3-phenyl-6-(o-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one, or

e. 5-methyl-3-phenyl-6-(m-tolyl)-isoxazolo[4,5-c]pyridin-4(5H)-one

there is obtained

a.5-methyl-3-(p-chlorophenyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

b.5-methyl-3-(p-fluorophenyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

c.5-methyl-3-(p-anisyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

d.5-methyl-3-phenyl-6-(o-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,or

e.5-methyl-3-phenyl-6-(m-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,respectively.

EXAMPLE 55-Methyl-3-phenyl-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one

A mixture of 21.2 g. of the product of Example 4, containing 62% of5-methyl-3-phenyl-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one0.0332 mole of bromo compound) and 7.2 g. (0.160 mole) dimethylamine in300 ml. toluene is stirred overnight at room temperature. The mixture isfiltered and the solid washed with toluene and the solvent evaporated invacuo. The resulting solid is dissolved in methylene chloride andtreated with 2N hydrochloric acid, the precipitate is then filtered,washed with water and ether. The solid is then dissolved in methylenechloride and 2N sodium dioxide and the organic phases separated andwashed with water, dried over anhydrous magnesium sulfate, filtered andevaporated in vacuo to give5-methyl-3-phenyl-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one;m.p. 159°-161° C.

Following the above procedure and using in place of5-methyl-3-phenyl-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,an equivalent amount of

a.5-methyl-3-(p-chlorophenyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

b.5-methyl-3-(p-fluorophenyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

c.5-methyl-3-(p-anisyl)-6-(p-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

d.5-methyl-3-phenyl-6-(o-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,or

e.5-methyl-3-phenyl-6-(m-bromomethylphenyl)-isoxazolo[4,5-c]pyridin-4(5H)-on

there is obtained

a.5-methyl-3-(p-chlorophenyl)-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

b.5-methyl-3-(p-fluorophenyl)-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

c.5-methyl-3-(p-anisyl)-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

d.5-methyl-3-phenyl-6-(o-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,or

e.5-methyl-3-phenyl-6-(m-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,respectively.

Again following the above procedure and using in place of dimethylaminean equivalent amount of

f. methylamine,

g. N-methyl-piperazine,

h. piperidine, or

i. morpholine

there is obtained

f.5-methyl-3-phenyl-6-(p-[methylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

g.5-methyl-3-phenyl-6-(p-[N-methyl-piperazinomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,

h.5-methyl-3-phenyl-6-(p-[piperidinomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,or

i.5-methyl-3-phenyl-6-(p-[morpholinomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one,respectively.

The5-methyl-3-phenyl-6-(p-[dimethylaminomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-oneof this example is an effective hypolipidemic agent when orallyadministered to an animal suffering from lipidemia at a dosage of 150mg. four times per day.

What is claimed is:
 1. A compound of the formula ##STR11## where R₁represents straight chain lower alkyl, andR₂ and R₃ together with Nrepresent ##STR12## where X is O or N--CH₃, and R₄ is hydrogen, halohaving an atomic weight of about 19 to 36 or lower alkoxy, or apharmaceutically acceptable salt thereof.
 2. A compound of the formula##STR13## where R₂, R₃ and R₄ are as defined in claim 1, or apharmaceutically acceptable salt therof.
 3. The compound of claim 1which is5-methyl-3-phenyl-6-(p-[morpholinomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one.4. The compound of claim 1 which is5-methyl-3-phenyl-6-(p-[N-methyl-piperazinomethyl]phenyl)-isoxazolo[4,5-c]pyridin-4(5H)-one.